Kidney Disease
Kidney disease refers to a range of conditions that impair the kidneys’ ability to filter waste products from the blood, regulate blood pressure, produce hormones, and maintain electrolyte balance. These vital organs play a crucial role in overall health, and their dysfunction can lead to serious systemic complications affecting nearly every part of the body.
The biological basis of kidney disease is complex, involving interactions between environmental factors, lifestyle choices, and an individual’s genetic makeup. Genetic variations, such as single nucleotide polymorphisms (SNPs), can influence an individual’s susceptibility to developing kidney disease or affect its progression. Research has identified[1]multiple genetic loci associated with various indices of renal function and chronic kidney disease. Understanding these genetic underpinnings can provide insights into disease mechanisms and potential therapeutic targets.
Clinically, kidney disease can manifest in various forms, from acute kidney injury to chronic kidney disease (CKD), which often progresses silently over many years. Early detection is critical, as advanced kidney disease can lead to kidney failure, necessitating lifelong interventions such as dialysis or kidney transplantation. Identifying individuals at higher genetic risk may allow for earlier preventative strategies, more targeted surveillance, and personalized management approaches to slow disease progression.
From a societal perspective, kidney disease represents a significant global public health challenge. It contributes substantially to morbidity and mortality, severely diminishing the quality of life for affected individuals and their families. Furthermore, the long-term care requirements and high costs associated with advanced treatments place a considerable burden on healthcare systems worldwide. Investigating the genetic factors involved in kidney disease is therefore of immense social importance, offering avenues for improved diagnosis, risk stratification, and the development of more effective treatments to alleviate this widespread burden.
Limitations
Section titled “Limitations”Understanding the genetic underpinnings of kidney disease through genome-wide association studies (GWAS) is subject to several important limitations that influence the interpretation and generalizability of findings. These limitations span methodological design, population representation, and the inherent complexity of disease etiology.
Methodological and Statistical Considerations
Section titled “Methodological and Statistical Considerations”Many genome-wide association studies face limitations regarding sample size and statistical power, particularly for complex diseases. Initial GWAS phases may have only approximately 50% power to detect moderate effect sizes, which reflects the inherent difficulties in recruiting sufficient participants, especially when phenotypes are clinically defined[2]. This modest power necessitates a staged study design, involving discovery and replication cohorts, to reduce the risk of false positives and confirm associations [2]. Consequently, the absence of a strong association signal does not definitively exclude a gene, as inadequate power or insufficient replication can mask genuine, but subtle, genetic effects [3]. It is critical that replication studies are performed to confirm associations and determine the range of associated phenotypes [3].
The comprehensiveness of genomic coverage also presents a limitation, as current genotyping arrays may not fully capture all common genetic variations and often have poor coverage of rarer variants, including structural variants [3]. This incomplete coverage reduces the power to detect less common but potentially penetrant alleles [3]. Furthermore, rigorous quality control is paramount in large datasets to prevent systematic differences or poor genotype calling from obscuring true associations or generating spurious findings [3]. The potential for population structure or cryptic population admixture to undermine inferences in case-control studies also requires careful analysis and control measures [3].
Generalizability and Phenotypic Definition
Section titled “Generalizability and Phenotypic Definition”The generalizability of findings from genetic studies can be limited by the demographic characteristics of the study populations. Many large-scale GWAS have predominantly recruited participants from specific ancestral backgrounds, such as Caucasian populations [2]. While this approach can reduce the risk of spurious associations due to population stratification within the study, it simultaneously restricts the direct applicability of the identified genetic associations to other diverse populations [2]. Therefore, the relevance of these susceptibility loci to individuals of non-European descent remains to be fully elucidated, impacting the broader understanding of disease etiology across global populations.
Defining complex phenotypes like kidney disease can be challenging, as they are often clinically ascertained and can involve a spectrum of presentations[2]. This clinical definition can introduce heterogeneity that may dilute genetic signals or make recruitment difficult, especially for rarer manifestations [2]. Additionally, measurement concerns arise from the genotyping process itself; employing different genotyping technologies across discovery, replication, and fine-mapping stages is a strategy to mitigate spurious associations stemming from genotyping errors [2]. However, the inherent limitations of genotyping platforms, such as less-than-complete coverage of common variation or poor coverage of rare variants, can still affect the comprehensive identification of disease-associated loci[3].
Remaining Knowledge Gaps and Complex Etiology
Section titled “Remaining Knowledge Gaps and Complex Etiology”Despite significant advancements in identifying genetic risk factors, the current understanding of kidney disease etiology remains incomplete. Many susceptibility effects are yet to be uncovered, and the identified genetic variants often explain only a fraction of the heritability, indicating substantial “missing heritability”[3]. This gap suggests that numerous other genetic factors, potentially including rare variants, structural variants, or complex gene-gene and gene-environment interactions, contribute to disease risk but are not fully captured by current approaches[3]. Consequently, the failure to detect a prominent association signal for a specific gene does not conclusively exclude its involvement, as current methodologies may lack the power or scope to identify all contributing factors [3].
While genetic studies reveal associations, translating these findings into clinically useful prediction of disease remains a significant challenge[3]. The identified genetic loci, either singly or in combination, have not yet provided substantial predictive power for individual risk assessment [3]. Furthermore, the complex interplay between genetic predispositions and environmental factors, though not always explicitly detailed in genetic association studies, is crucial for understanding disease development. Unaccounted environmental confounders or unmeasured gene-environment interactions can influence disease penetrance and expression, leading to an incomplete picture of the overall risk architecture and limiting the development of comprehensive prevention or treatment strategies.
Variants
Section titled “Variants”Genetic variants play a crucial role in influencing an individual’s susceptibility to kidney disease and impacting various aspects of renal function. These single nucleotide polymorphisms (SNPs) can alter gene expression, protein function, or regulatory pathways, leading to diverse health implications. Understanding these genetic associations provides insights into disease mechanisms and potential targets for prevention and treatment.
Variants within the UMOD (Uromodulin) gene, such as rs36060036 , are strongly linked to kidney function and chronic kidney disease (CKD) risk. UMOD encodes Tamm-Horsfall protein, the most abundant protein found in human urine, which is exclusively produced in the renal tubular cells of the thick ascending limb of the loop of Henle. This protein is thought to protect against inflammation and infection within the kidney and may have a role in renal development[1]. Rare mutations in UMOD are known to cause Mendelian forms of kidney disease, including medullary cystic kidney disease type 2 and familial juvenile hyperuricemic nephropathy[1]. Common variants in this gene can influence estimated Glomerular Filtration Rate (eGFR), with certain alleles, like the T allele of rs12917707 (a variant in high linkage disequilibrium with rs36060036 ), being associated with a reduced risk of CKD and better overall kidney function over time [1]. These findings highlight the loop of Henle as a critical region for CKD pathogenesis.
The APOL1 (Apolipoprotein L1) gene, with variants like rs73885319 , rs60910145 , and rs58384577 , represents a significant genetic determinant of kidney disease, particularly in populations of African ancestry. APOL1 proteins are involved in innate immunity and lipid metabolism, and specific risk alleles (G1 and G2) are associated with a substantially increased risk for various kidney conditions, including focal segmental glomerulosclerosis (FSGS), HIV-associated nephropathy, and hypertension-attributed nephropathy. These variants are believed to have persisted due to their protective effect against trypanosomal infections, demonstrating a complex interplay between host defense and kidney health. While the precise mechanisms by which APOL1 risk variants lead to kidney damage are still being researched, it is understood that they contribute to cellular toxicity and inflammation within renal cells, underscoring the importance of common genetic variants influencing renal function and disease[1].
Other genetic regions also contribute to kidney health through various biological pathways. Variants in FTO(Fat Mass and Obesity-associated), such asrs11642015 and rs1421085 , are primarily known for their strong association with obesity and type 2 diabetes. Given that obesity and diabetes are major risk factors for chronic kidney disease, FTO variants can indirectly influence kidney health by predisposing individuals to these metabolic conditions. Similarly, the region encompassingMTCO3P1 - HLA-DQB3, with variants like rs9275596 , involves genes critical for immune system function. HLA genes are central to immune responses, and variations can influence susceptibility to autoimmune diseases that often affect the kidneys, such as lupus nephritis. The PRDM8 - FGF5 region, including variants like rs10857147 , involves genes with roles in transcription regulation and cell growth signaling, respectively. While specific kidney associations for these variants are still being elucidated, disruptions in such fundamental cellular processes can have broad implications for kidney development and function, suggesting that additional yet undiscovered genetic variants impact variability in renal function [1].
Several additional genes and their variants contribute to the intricate genetic landscape of kidney disease.PDILT (Protein Disulfide Isomerase Like, Testis-expressed) and its variant rs77924615 are involved in protein folding within the endoplasmic reticulum, a process essential for the proper function of many kidney proteins. Dysregulation here can lead to ER stress, contributing to renal pathology. CDH12 (Cadherin 12) and the adjacent Y_RNA region, with variant rs569199361 , relate to cell adhesion and non-coding RNA regulation, both vital for maintaining the structural integrity and function of kidney tissues. LINC02955, a long intergenic non-coding RNA, with variant rs558702440 , likely plays a regulatory role in gene expression, and its disruption could affect pathways relevant to kidney development or disease. Furthermore,STARD13 (StAR-Related Lipid Transfer Domain Containing 13) with rs182226781 , and ACAP2 (ArfGAP With Coiled-Coil And Ankyrin Repeat Domains 2) with rs112341402 , are involved in lipid metabolism, cytoskeletal dynamics, and membrane trafficking. These cellular processes are fundamental for the specialized functions of kidney cells, such as filtration and reabsorption, and their perturbation can contribute to kidney dysfunction, highlighting that common genetic variants influence renal function and disease[1].
Key Variants
Section titled “Key Variants”| RS ID | Gene | Related Traits |
|---|---|---|
| rs36060036 | UMOD | CD27 antigen measurement corneodesmosin measurement trefoil factor 3 measurement tgf-beta receptor type-2 measurement thrombomodulin measurement |
| rs10857147 | PRDM8 - FGF5 | glomerular filtration rate coronary artery disease systolic blood pressure diastolic blood pressure pulse pressure measurement |
| rs77924615 | PDILT | glomerular filtration rate chronic kidney disease blood urea nitrogen amount serum creatinine amount protein measurement |
| rs11642015 rs1421085 | FTO | diastolic blood pressure systolic blood pressure pulse pressure measurement mean arterial pressure blood urea nitrogen amount |
| rs9275596 | MTCO3P1 - HLA-DQB3 | kidney disease IGA glomerulonephritis peanut allergy measurement omega-6 polyunsaturated fatty acid measurement |
| rs73885319 rs60910145 rs58384577 | APOL1 | chronic kidney disease focal segmental glomerulosclerosis glomerular filtration rate Proteinuria serum creatinine amount |
| rs569199361 | CDH12 - Y_RNA | kidney disease |
| rs558702440 | LINC02955 | kidney disease |
| rs182226781 | STARD13 | kidney disease |
| rs112341402 | ACAP2 | kidney disease |
Defining Chronic Kidney Disease and Renal Function
Section titled “Defining Chronic Kidney Disease and Renal Function”Chronic Kidney Disease (CKD) is precisely defined by specific diagnostic criteria, providing a clear operational framework for its identification. A commonly used definition for CKD establishes the condition as an estimated Glomerular Filtration Rate (eGFR) based on creatinine (eGFRcrea) below 60 ml/min/1.73m².[1]. This threshold, adopted from national guidelines, serves as a critical diagnostic criterion, distinguishing individuals with impaired kidney function from those with healthy renal function. The conceptual framework for CKD hinges on a sustained reduction in the kidneys’ ability to filter waste products from the blood, a function quantified by GFR.
Renal function, broadly, refers to the physiological capabilities of the kidneys, particularly their filtration capacity. The term “indices of renal function” encompasses various measures and indicators reflecting kidney health and performance. These indices are crucial for both clinical diagnosis and research, allowing for the assessment of disease presence and progression. The standardized definition of CKD facilitates consistent identification and classification across different clinical settings and research studies, enabling comparable data collection and analysis.
Measurement Approaches and Biomarkers
Section titled “Measurement Approaches and Biomarkers”The assessment of renal function relies on specific measurement approaches, primarily through estimating the Glomerular Filtration Rate (GFR) using various biomarkers. Two commonly employed methods involve estimating GFR using creatinine (eGFRcrea) and cystatin C (eGFRcys). [1]. These estimations are derived from established equations that integrate biomarker levels with other patient characteristics. While population-based measures of GFR are acknowledged as imperfect, the utilization of multiple biomarkers like creatinine and cystatin C can enhance the accuracy and reliability of detecting true signals of kidney impairment. [1].
The diagnostic threshold for CKD, specifically an eGFRcrea less than 60 ml/min/1.73m², functions as a critical cut-off value for classifying disease severity.[1]. This threshold is integral to severity gradations, allowing clinicians and researchers to categorize the extent of kidney damage. The use of these standardized biomarkers and thresholds ensures a consistent approach to diagnosing and monitoring kidney disease, which is vital for both individual patient management and large-scale epidemiological studies, such as genome-wide association studies investigating genetic correlates of disease.
Terminology and Classification Systems
Section titled “Terminology and Classification Systems”Key terminology in the context of kidney disease includes “Chronic Kidney Disease” (CKD), which represents the overarching diagnostic classification for persistent kidney dysfunction. Terms like “eGFRcrea” and “eGFRcys” are standardized nomenclature referring to estimated Glomerular Filtration Rate based on creatinine and cystatin C, respectively, serving as essential metrics for assessing renal health. These terms form part of a structured vocabulary crucial for clear communication in nephrology. The classification of kidney disease, particularly CKD, largely follows a categorical approach based on eGFR thresholds, defining distinct stages of severity.
This nosological system, which defines CKD based on an eGFRcrea below a specific value, allows for a consistent disease classification and facilitates the study of its genetic underpinnings. For instance, research endeavors often focus on identifying genetic loci associated with “indices of renal function” or the presence of “chronic kidney disease” as defined by these criteria. This structured classification, rooted in measurable biomarkers and defined thresholds, is fundamental for understanding disease etiology, tracking progression, and developing targeted interventions.
There is no information about kidney disease in the provided research.
Causes
Section titled “Causes”Kidney disease, particularly chronic kidney disease, is a complex condition influenced by a variety of interacting factors that contribute to its onset and progression. While specific mechanisms can vary, genetic predisposition plays a significant role in determining an individual’s susceptibility.
Inherited Genetic Susceptibility
Section titled “Inherited Genetic Susceptibility”A significant causal factor in kidney disease involves inherited genetic susceptibility. Research has identified multiple novel loci that are directly associated with an individual’s risk of developing chronic kidney disease[1]. These specific inherited variants contribute to a predisposition, meaning individuals carrying certain genetic profiles may be inherently more vulnerable to the condition. Such genetic markers provide insights into the underlying biological pathways that, when disrupted, can lead to kidney dysfunction.
Polygenic Risk and Complex Disease Architecture
Section titled “Polygenic Risk and Complex Disease Architecture”Kidney disease often exhibits a complex, polygenic architecture, where the cumulative effect of several distinct genetic loci, rather than a single gene, contributes to disease risk[1]. This polygenic nature implies that numerous common genetic variants, each with a small individual effect, collectively increase an individual’s overall susceptibility. Understanding these complex interactions among multiple genes is essential for fully mapping the genetic landscape of kidney disease and predicting individual risk profiles.
Genetic Regulation of Renal Function
Section titled “Genetic Regulation of Renal Function”The identified genetic loci exert their influence by affecting various indices of renal function, which are key indicators of kidney health [1]. These genetic influences can impact processes such as filtration, reabsorption, and secretion, critical functions performed by the kidneys. Variations in these genes can lead to suboptimal kidney performance over time, thereby increasing the likelihood of developing chronic kidney disease through impaired physiological regulation.
Pathways and Mechanisms
Section titled “Pathways and Mechanisms”The pathogenesis of kidney disease involves a complex interplay of molecular pathways and regulatory mechanisms that, when dysregulated, impair renal function and lead to chronic conditions. Genetic predispositions, identified through studies, highlight key areas where these pathways may be compromised[1].
Genetic Regulation and Renal Homeostasis
Section titled “Genetic Regulation and Renal Homeostasis”The identification of multiple genetic loci associated with indices of renal function and chronic kidney disease underscores the critical role of gene regulation in maintaining kidney homeostasis[1]. These specific loci likely influence the expression and function of genes vital for kidney health, thereby impacting the intricate balance of cellular processes within renal cells. Dysregulation stemming from these genetic variations can lead to altered gene transcription and translation, affecting the synthesis of proteins involved in structural integrity, solute transport, or the initiation of essential intracellular signaling cascades. This disruption can compromise the kidney’s ability to filter waste and maintain fluid and electrolyte balance, contributing to disease onset.
Systems-Level Dysregulation in Kidney Disease
Section titled “Systems-Level Dysregulation in Kidney Disease”The involvement of multiple genetic loci in chronic kidney disease suggests a complex interplay of various biological pathways, emphasizing the importance of systems-level integration where pathway crosstalk and network interactions are crucial[1]. Genetic variations at these loci can perturb interconnected molecular networks, leading to a cascade of effects across different cellular compartments and functions within the kidney. Such extensive dysregulation can trigger compensatory mechanisms, which, while initially protective, may ultimately contribute to disease progression and the emergent properties of chronic renal dysfunction over time. Understanding these network interactions is key to unraveling the full scope of kidney disease pathogenesis.
Molecular Mechanisms and Therapeutic Implications
Section titled “Molecular Mechanisms and Therapeutic Implications”The impact of genetic loci on renal function and chronic kidney disease extends to fundamental molecular mechanisms, where variations could influence protein modification, post-translational regulation, and allosteric control of key enzymes[1]. Changes in these regulatory processes can alter protein activity, stability, and interactions, thereby affecting the overall flux through metabolic or signaling pathways critical for kidney cell viability and function. Identifying these specific dysregulated molecular mechanisms and the proteins involved provides potential therapeutic targets for interventions aimed at restoring renal homeostasis or slowing disease progression, offering avenues for precision medicine approaches.
Clinical Relevance
Section titled “Clinical Relevance”Genetic Insights in Risk Assessment and Prognosis
Section titled “Genetic Insights in Risk Assessment and Prognosis”Genetic studies, including genome-wide association analyses, have identified multiple genetic loci associated with indices of renal function and chronic kidney disease (CKD)[1]. These findings are crucial for enhancing risk assessment, allowing for the identification of individuals at higher genetic predisposition to developing kidney disease. Such genetic insights can provide prognostic value by predicting disease progression and long-term outcomes, potentially guiding early intervention strategies. The identification of these loci contributes to a deeper understanding of the genetic architecture underlying kidney disease, moving towards more precise diagnostic and predictive tools.
Comorbidities and Integrated Disease Management
Section titled “Comorbidities and Integrated Disease Management”Kidney disease frequently coexists with and contributes to the progression of other significant health conditions, highlighting the importance of integrated disease management. Genetic studies have identified shared genetic susceptibilities between kidney function and cardiovascular diseases, such as coronary artery disease and subclinical atherosclerosis[4], [5], [6], [7]. This overlap suggests that managing kidney disease must consider its systemic implications, particularly regarding cardiovascular health. Understanding these comorbidities allows clinicians to tailor treatment selection and monitoring strategies to address the complex interplay of conditions, aiming to mitigate complications and improve overall patient outcomes.
Advancing Personalized Medicine and Prevention Strategies
Section titled “Advancing Personalized Medicine and Prevention Strategies”The identification of specific genetic loci associated with kidney disease paves the way for personalized medicine approaches. By understanding an individual’s genetic profile, clinicians can potentially develop tailored prevention strategies, particularly for those identified as high-risk[1]. While the exact clinical utility of genetic markers for clinically useful disease prediction is still evolving[3], these findings represent a foundational step towards identifying specific pathways for targeted interventions. This approach aims to move beyond generalized treatments to interventions that are more effective and precisely suited to an individual’s unique genetic and clinical characteristics, thereby enhancing the efficacy of preventive measures and treatment responses.
Frequently Asked Questions About Kidney Disease
Section titled “Frequently Asked Questions About Kidney Disease”These questions address the most important and specific aspects of kidney disease based on current genetic research.
1. Why do some in my family get kidney disease but others don’t?
Section titled “1. Why do some in my family get kidney disease but others don’t?”It’s a complex mix of genetics and other factors. Even with shared family genes, individual genetic variations, lifestyle choices, and environmental exposures differ significantly. Your specific genetic makeup might offer some protection or increase risk compared to a sibling, even if you share many genes.
2. Can healthy habits really prevent kidney disease if it runs in my family?
Section titled “2. Can healthy habits really prevent kidney disease if it runs in my family?”Yes, absolutely! While genetics play a role in susceptibility, your lifestyle choices – like diet and exercise – are crucial. They interact with your genes. Adopting healthy habits can significantly influence your risk, potentially slowing progression or even helping prevent the disease, even if you have a family history.
3. Should I get a DNA test to check my kidney disease risk?
Section titled “3. Should I get a DNA test to check my kidney disease risk?”It depends. Genetic tests can identify some variations associated with higher risk, which might guide earlier preventative strategies or more targeted surveillance. However, current genetic markers don’t fully predict who will get kidney disease, as they only explain a fraction of the overall risk. It’s best to discuss this with your doctor.
4. Does my family’s background affect my kidney disease risk?
Section titled “4. Does my family’s background affect my kidney disease risk?”Yes, it can. Genetic studies have shown that certain genetic risk factors for kidney disease might be more common or have different effects in specific ancestral populations. Since much research has focused on people of European descent, the full picture for other backgrounds is still being understood. Your ethnic background could influence your specific genetic risks.
5. Why does my kidney disease seem to get worse faster than others?
Section titled “5. Why does my kidney disease seem to get worse faster than others?”Your individual genetic makeup can influence how quickly kidney disease progresses. Beyond genetics, factors like your diet, blood pressure control, and other health conditions also play a big role. It’s a complex interaction between your genes and these environmental and lifestyle factors that determines the pace of the disease.
6. My doctor says I have kidney disease, but I feel totally fine. How?
Section titled “6. My doctor says I have kidney disease, but I feel totally fine. How?”Kidney disease, especially chronic forms, can progress silently for a long time without noticeable symptoms. Your kidneys are very resilient and can function well even when damaged. That’s why early detection through routine check-ups is so important, allowing for interventions before serious problems arise.
7. Why did my friend get kidney disease, but I didn’t, living similarly?
Section titled “7. Why did my friend get kidney disease, but I didn’t, living similarly?”Even if you share similar lifestyles, your genetic makeup is unique. Genetic variations can make one person more susceptible to kidney disease than another, even with similar environmental exposures. It highlights how your genes interact with everything else to determine your individual risk.
8. Is there more to my kidney disease risk than what my doctor says?
Section titled “8. Is there more to my kidney disease risk than what my doctor says?”Yes, likely. While doctors rely on known risk factors, our understanding of kidney disease genetics is still growing. There are likely many other genetic factors, including rare variants or complex interactions between genes and the environment, that contribute to risk but haven’t been fully identified yet.
9. Can a genetic test tell me for sure if I’ll get kidney disease?
Section titled “9. Can a genetic test tell me for sure if I’ll get kidney disease?”Not definitively. While genetic tests can identify some variants linked to higher risk, they don’t provide a sure prediction. Kidney disease is complex, influenced by many genetic, lifestyle, and environmental factors. Current tests explain only a fraction of the overall risk and can’t say for certain if you will develop the disease.
10. Can I overcome my family’s kidney history with diet and exercise?
Section titled “10. Can I overcome my family’s kidney history with diet and exercise?”You absolutely can make a significant difference! While you inherit certain genetic predispositions, your lifestyle choices like diet and exercise play a powerful role. These habits interact with your genes and can help mitigate genetic risks, slow progression, and improve your overall kidney health, even with a family history.
This FAQ was automatically generated based on current genetic research and may be updated as new information becomes available.
Disclaimer: This information is for educational purposes only and should not be used as a substitute for professional medical advice. Always consult with a healthcare provider for personalized medical guidance.
References
Section titled “References”[1] Köttgen, Anna, et al. “Multiple loci associated with indices of renal function and chronic kidney disease.”Nature Genetics, vol. 41, no. 6, 2009, pp. 712-717. PMID: 19430482.
[2] Burgner D, et al. “A genome-wide association study identifies novel and functionally related susceptibility Loci for Kawasaki disease.”PLoS Genet, 2009.
[3] Wellcome Trust Case Control Consortium. “Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.” Nature, vol. 447, no. 7145, 2007, pp. 661-678.
[4] Samani, N. J., et al. “Genomewide association analysis of coronary artery disease.”N Engl J Med, vol. 357, no. 5, 2007, pp. 443-453.
[5] Erdmann, Jeanette, et al. “New susceptibility locus for coronary artery disease on chromosome 3q22.3.”Nature Genetics, vol. 41, no. 3, 2009, pp. 280-282. PMID: 19198612.
[6] O’Donnell, Christopher J., et al. “Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI’s Framingham Heart Study.”BMC Medical Genetics, vol. 8, suppl. 1, 2007, p. S4. PMID: 17903303.
[7] Larson, Martin G., et al. “Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes.”BMC Medical Genetics, vol. 8, suppl. 1, 2007, p. S5. PMID: 17903304.